Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation

Abstract

The sigma-2 (σ(2)) receptor is a potential biomarker of proliferative status of solid tumors. Specific synthetic probes using N-substituted-9-azabicyclo [3.3.1]nonan-3α-yl carbamate analogs have been designed and implemented for experimental cancer diagnosis and therapy. We employed the fluorescently labeled σ(2) receptor probe, SW120, to evaluate σ(2) receptor expression in human stem cells (SC), including: bone marrow stromal, neural progenitor, amniotic fluid, hematopoetic, and embryonic stem cells. We concurrently evaluated the intensity of SW120 and 5-ethynyl-2'-deoxyuridine (EdU) relative to passage number and multi-potency. We substantiated significantly higher σ(2) receptor density among proliferating SC relative to lineage-restricted cell types. Additionally, cellular internalization of the σ(2) receptor in SC was consistent with receptor-mediated endocytosis and confocal microscopy indicated SW120 specific co-localization with a fluorescent marker of lysosomes in all SC imaged. These results suggest that σ(2) receptors may serve to monitor stem cell differentiation in future experimental studies.